HIV infection is accompanied by elevated levels of prostaglandins which can modulate immune function by inhibiting lymphokine production, T-cell function, and T and B cell proliferation. The full length gp-120 recombinant expressed in CHO cells was isolated and purified. The gp-120 stimulated K+ channel activity in rat astrocytes and induced the expression of the cell adhesion molecule, ICAM, in primary cultures of astrocytes. An antibody (OKT4A) which binds to the CD4 receptor stimulates the formation of prostaglandins and cytokines from monocytes. OKT4A greatly enhanced p56lck autophosphorylation while the CHO expressed gp-120 produced a marginal increase in p56lck tyrosine phosphorylation. THP-1 cells and THP-1 cells induced to differentiate into macrophages by TPA treatment were incubated with gp-120, OKT4A or LPS (a known stimulator of PGHS-2 expression in monocytes/macrophages). Both the gp- 120 and the OKT4A antibody failed to increase either the release of arachidonic acid or the formation of prostaglandins. Western and Northern analysis indicated the presence of PGHS-1 in these monocytes. LPS stimulated an increase in PGHS-2 mRNA and protein in the TPA-treated cells but not in the monocytes. The expression of PGHS-1 and -2 protein and message was not increased by incubation of the control or TPA- differentiated cells with either the gp-120 or OKT4A antibody. The observation that gp-120 preparations and/or OKT4A, which have biological activity in other systems, do not enhance prostaglandin formation in human monocytes/macrophages provides evidence that the interaction of the envelope protein with the CD4 receptor is not responsible for the increase in prostaglandins observed in HIV-1 infected persons.